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Variation in the α 5 nicotinic acetylcholine receptor subunit gene predicts cigarette smoking intensity as a function of nicotine content

The Pharmacogenomics Journal volume 14, pages 70–76 (2014)Cite this article

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Abstract

A single-nucleotide polymorphism (SNP) in the α5 nicotinic acetylcholine receptor subunit gene, rs16969968, has been repeatedly associated with both smoking and respiratory health phenotypes. However, there remains considerable debate as to whether associations with lung cancer are mediated through effects on smoking behavior. Preclinical studies suggest that α5 receptor subunit expression and function may have a direct role in nicotine titration during self administration. The present study investigated the association of CHRNA5 polymorphisms and smoking topography in 66 smokers asked to smoke four nicotine-containing (nicotine yield=0.60 mg) and four placebo (nicotine yield <0.05 mg) cigarettes, during separate experimental sessions. Genotype at rs16969968 predicted nicotine titration, with homozygotes for the major allele (G:G) displaying significantly reduced puff volume in response to nicotine, whereas minor allele carriers (A:G or A:A) produced equivalent puff volumes for placebo and nicotine cigarettes. The present results suggest that puff volume may be a more powerful objective phenotype of smoking behavior than self-reported cigarettes per day and nicotine dependence. Further, these results suggest that the association between rs16969968 and lung cancer may be mediated by the quantity of smoke inhaled.

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Acknowledgements

This study was funded by NIH grants R21 DA027001, R21 DA024226 and R25 CA090314. The authors would like to thank Renee Ornduff and Natasha Garcia for their work on the project.

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Authors and Affiliations

  1. University of South Florida, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    D A MacQueen, B W Heckman, M D Blank, K Janse Van Rensburg, J Y Park, D J Drobes & D E Evans

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  1. D A MacQueen
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  2. B W Heckman
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Correspondence to D E Evans.

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MacQueen, D., Heckman, B., Blank, M. et al. Variation in the α 5 nicotinic acetylcholine receptor subunit gene predicts cigarette smoking intensity as a function of nicotine content. Pharmacogenomics J 14, 70–76 (2014). https://doi.org/10.1038/tpj.2012.50

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